Remissions ("cures") were induced in BALB/c plasma cell tumor-bearing mice treated with various drugs singly and in combination. The most effective chemotherapy not only yielded a higher proportion of "cures" but also rendered them comparatively more resistant to consecutive challenges with increasing numbers of isogeneic tumor cells. The objectives of the proposed research are: to identify the immune mechanism(s) involved in the development of resistance to the tumor, to define their contribution to the therapeutic effects of the drugs, and to determine the possibly selective effects of the individual drugs on host immune mechanisms which lead to the establishment of the resistance to the tumor. Clarification is to be accomplished by testing for cell-mediated, complement-dependent, and antibody-mediated cellular cytolysis of 51Cr-labeled target tumor cells incubated in vitro with peritoneal exudate, spleen and lymph node cells, or with antiserum from unchallenged and challenged cured mice. The latter two objectives will be elucidated by measuring drug effects on immune reactivities of mice treated with different drugs and dose regimens, and by experiments in in vivo transfer of immunity. The derived information may provide a rationale for selecting from a group of effective drugs those with greater potential to induce both remission and establishment of immunity to tumor.